**4. The landmark trials of CEA versus medical therapy; NASCET, ACAS and ECST**

The role of CEA in prevention of stroke was established based on large randomized trials performed mostly in the early 1990s.

This meta-analysis of ECST and NASCET trials showed that surgery increased the 5-year risk of ipsilateral ischemic stroke in patients with <30% stenosis (absolute risk reduction of –2.2%, P = 0.05), had no effect in patients with 30-49% stenosis (absolute risk reduction of 3.2%, P = 0.6), was of marginal benefit in those with 50% to 69% stenosis (absolute risk reduction of 4.6%, P =0.04), and was highly beneficial in those with ≥70% stenosis with‐ out near-occlusion (absolute risk reduction of 16.0%, P < 0.001). There was a trend toward benefit from surgery in patients with near occlusion at 2 years' follow up (absolute risk

reduction of 5.6%, P = 0.19), but no benefit at 5 years (absolute risk reduction of –1.7%, P =0.9). Both ACST and ACAS studies showed benefit from CEA in >60% asymptomatic stenosis. However, neither showed increasing benefit from surgery with increasing degree

**Table 1.** Number needed to treat by endarterectomy to prevent one stroke in 2 years in patients with carotid stenosis

**No of patients in specified trial**

ACE 2848

ACE=aspirin and carotid endarterectomy trial.

1.2% risk is assumed for the ACE patients and VA patients.

§No medical arm—assumed from ACAS data.

treatment alone.

\*\*By NASCET measurement.

†Extrapolated from results.

**Medical risk (%) at 2 years**

**Surgical risk (%) at 2 years**

**Symptomatic patients** 70-99% NASCET 659 21.4 8.6 12.8 60 8 5.8 70-99%ECST\*\* 501 19.9 7.0 12.9 65 8 5.6 50-69% NASCET 858 14.2 9.2 5.0 35 20 7.1 50-69% ECST\*\* 684 9.7 11.1 -1.4 -14 - 9.8 <50%NASCET 1368 11.6 10.1 1.5 13 67 6.5 <50% ECST\*\* 1882 4.3 9.5 -5.2 -109 - 6.1 **Asymptomatic patients** ≥50%, VA, men only 444 7.7**†** 5.6**†** 2.1 27 48 4.4

ACAS 1662 5.0 3.8*‡* (actual) 1.2 24 83 2.6

\*NNT = Number needed to treat by CEA to prevent one stroke in 2 years after the procedure, compared with medical

‡Assigning a perioperative risk of 2.6% based on 724 of 825 patients who actually received endarterectomy in the surgical arm of ACAS, and utilizing the 0.6% risk of stroke in each of the two years after endarterectomy. The same

5.0**§ (assumed)** **Risk difference**

**(%)** **Relative risk reduction (%)**

5.8 -0.8 - - 4.6

**No need to treat\***

**Perioperative stroke**

**and death rate (%)**

107

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Update on Carotid Revascularization: Evidence from Large Clinical Trials


ACE=aspirin and carotid endarterectomy trial.

\*NNT = Number needed to treat by CEA to prevent one stroke in 2 years after the procedure, compared with medical treatment alone.

\*\*By NASCET measurement.

be considered in the hemodynamically unstable patient or in situations where general

Early attempts at reconstruction of the carotid artery at the bifurcation were carried out by Carrea, Molins, and Murphy in 1951 and subsequently by Eastcott, Pickering, and Robb in 1954. In 1965 DeBakey reported that he performed the first CEA in 1953. Although not published, there is controversy about this claim.[1] Subsequently, a group of neurologists, vascular surgeons, and neurological surgeons performed a study on the "new technique" comparing it with medical therapy. Interestingly, the surgical mortality was surgical mortality of 4.5% in 2400 operations. This early study the study delineated careful methods of measuring common carotid and internal carotid and vertebral artery stenosis. The study also determined the upper level of ready surgical accessibility as well as the contraindications to the operation. [2] Additionally, myocardial infarction was identified as the principal cause of late mortality in those patients undergoing successful surgical treatment. Providing the patients survived the surgical therapy, the occurrence of new stroke was 4% in the surgical group. However, the superiority of surgery over medical therapy was not definitive. Despite criticism, CEA became extremely popular. It became the most commonly performed peripheral arterial procedure in the United States, reaching a peak of 107,000 operations in nonveteran hospitals in the United States in 1985.[1] At that time, however, neurologists were skeptical. Their fears were sup‐ ported by reports that the rates of death or stroke from CEA were 10%. Endarterectomy turned from a great procedure to an operation "that has escaped critical analysis to be let loose on an unsuspecting public"![3] These concerns stressed the need to perform well-designed random‐ ized trials under independent neurological audit. Those trials established the role of CEA

**4. The landmark trials of CEA versus medical therapy; NASCET, ACAS and**

The role of CEA in prevention of stroke was established based on large randomized trials

This meta-analysis of ECST and NASCET trials showed that surgery increased the 5-year risk of ipsilateral ischemic stroke in patients with <30% stenosis (absolute risk reduction of –2.2%, P = 0.05), had no effect in patients with 30-49% stenosis (absolute risk reduction of 3.2%, P = 0.6), was of marginal benefit in those with 50% to 69% stenosis (absolute risk reduction of 4.6%, P =0.04), and was highly beneficial in those with ≥70% stenosis with‐ out near-occlusion (absolute risk reduction of 16.0%, P < 0.001). There was a trend toward benefit from surgery in patients with near occlusion at 2 years' follow up (absolute risk

anesthesia may be too risky.

106 Carotid Artery Disease - From Bench to Bedside and Beyond

**3. The early years of carotid endarterectomy**

versus medical treatment for stroke prevention.

performed mostly in the early 1990s.

**ECST**

†Extrapolated from results.

‡Assigning a perioperative risk of 2.6% based on 724 of 825 patients who actually received endarterectomy in the surgical arm of ACAS, and utilizing the 0.6% risk of stroke in each of the two years after endarterectomy. The same

1.2% risk is assumed for the ACE patients and VA patients.

§No medical arm—assumed from ACAS data.

**Table 1.** Number needed to treat by endarterectomy to prevent one stroke in 2 years in patients with carotid stenosis

reduction of 5.6%, P = 0.19), but no benefit at 5 years (absolute risk reduction of –1.7%, P =0.9). Both ACST and ACAS studies showed benefit from CEA in >60% asymptomatic stenosis. However, neither showed increasing benefit from surgery with increasing degree

of stenosis. This observation was assumed to be attributable to a lack of statistical power of the trials. The benefit from CEA relates to the complication rates. Reported benefits were predicated on operative risks of stroke or death of 7.5% in the ECST and 6.5% in the NASCET. If the disabling stroke and death rates exceed this by as little as 2%, the benefit from CEA disappears.[4]

inconceivable at the end of the 1970s to apply their work to arteries supplying the brain. Klaus Mathias chose to ignore this strict limit and was able to successfully perform angioplasty of atherosclerotic stenoses at the carotid bifurcation in 1980.[7] The technique evolved slowly from simple balloon dilatation to involve stenting, used first by Théron in 1990 and then

While carotid endarterectomy was growing to maturity, anther contender was born. After the fundamental work in endovascular therapy by Charles Dotter and Andreas Grüntzig, it was inconceivable at the end of the 1970s to apply their work to arteries supplying the brain. Klaus Mathias chose to ignore this strict limit and was able to successfully perform angioplasty of atherosclerotic stenoses at the carotid bifurcation in 1980.[7] The technique evolved slowly from simple balloon dilatation to

> Roubin 146 210 37 99 NS 1 / 0.65 1.3 4.6 6 mo, ,5%; 12 mo, ID Theron 69 69 NS 100 NS … … … 4% (time not specified)

Diethrich 110 129 72 99.1 7.3 2 / 1.8% 2 4.5 6 mo, NS; 12

Yadav 107 189 36 100 7.9 1 / 0.9% 1.9 6.5 6 mo, 4.9%; 12

Vozzi 22 19 55 96 NS 1 / 4.5% 4.5 4.5 6 mo, NS; 12

Criado 33 NS 27 100 NS 0 0 0 3% (mean 8-mo

Wholey 108 NS 44 95 NS 2/ 1.9% 1.8 1.8 1% (mean 6-mo

Henry 163 178 35 99.4 NS 0/ .. 1.8 1.2 6 mo, 2.3%;

m 22 31 32 96.2 27.3 1 / 4.5% 13.6 9.0 6 mo, 14.3%;

Waigand 50 56 72 100 2 1 / 2% 2 2 8.7% (mean 8-

Bergeron 99 99 42 97 2.0 0/… 0 1 4.2% (mean 13-

The Global Carotid Artery Stent Registry: In 1998, Wholey et al collected data from major interventional centers worldwide as well as from peer-reviewed journals. The total number of procedures that have been performed till that date included 2,048 cases, with a technical success of 98.6%. The stroke rate was 3.08%. The 30-day post-procedure mortality rate was 1.37%. The registry was updated in 2003. The total number of stent procedures performed then became 12392 with a technical success rate of 98.9%. Overall, there was TIA rate of 3.07%, minor strokes of 2.14%, major strokes of 1.20%, and procedure-related deaths of 0.64%. There were 6753 cases done without protection and which incurred a 5.29% rate of strokes and procedure-related deaths. In the 4221 cases with cerebral protection, there was a 2.23% rate of strokes and procedure-related deaths. The rate of neurologic events was

The Global Carotid Artery Stent Registry: In 1998, Wholey et al collected data from major interventional centers worldwide as well as from peer-reviewed journals. The total number of

In the following years, several registries that were supported by the device industry were reported. These registries included

patients who are considered high risk for CEA because one or more of the following features:

**Minor Stroke** 

Update on Carotid Revascularization: Evidence from Large Clinical Trials

**Rate (%)** 

**Restenosis rate** 

http://dx.doi.org/10.5772/57153

109

mo, NS

mo, NS

mo, ID

follow-up)

follow-up)

12 mo, ID

12 mo, NS

mo follow-up

mo follow-up)

widespread use of cerebral protection devices.

**8. The initial case-series and registries of Carotid stenting** 

Teitelbau

**9. Results of multicenter registries** 

**Table 2.** Carotid Stent Series [8]

**9. Results of multicenter registries**

1.2%, 1.3%, and 1.7% at 1, 2, and 3 years, respectively.[9]

1. Class-III/IV congestive heart failure

2. Left ventricular ejection fraction<30%

3. Open heart surgery within 6 weeks

5. Unstable angina: class III/IV

4. Recent myocardial infarction (>24 h <30 d)

6. Concurrent requirement for coronary revascularization

Table 2. Carotid Stent Series [8]

**8. The initial case-series and registries of carotid stenting**

involve stenting, used first by Théron in 1990 and then widespread use of cerebral protection devices.

**Author No of Patients No of stents Asymptomatic stenosis (%) Technical success rates (%) 30-day Morbidity or Mortality (%) No of Deaths/ Mortality Rate Major Stroke Rate (%)** 
